Identification of novel Plasmodium gallinaceum zygote- and ookinete-expressed proteins as targets for blocking malaria transmission
Identification of novel Plasmodium gallinaceum zygote- and ookinete-expressed proteins as targets for blocking malaria transmission
复制标题
DOI：
10.1128/iai.70.1.102-106.2002
复制
发表时间：
2002-01-01
影响因子：
3.1
通讯作者：
Vinetz, JM
中科院分区：
文献类型：
--
作者：
Langer, RC;Li, FW;Vinetz, JM
研制阻断传播的疫苗是控制疟疾的一种办法。为了鉴定作为阻断疟疾传播的靶标的新的疟原虫合子和动合子分泌蛋白，产生针对在鸡疟原虫动合子培养上清液中发现的寄生虫分泌蛋白的单克隆抗体（MAbs）。根据寄生虫上的空间定位、抗原表达的时间过程和Western免疫印迹模式，鉴定了四种MAb-1A 6、2A 5、2B 5和4 B6-，其以不同模式与鸡疟原虫合子和动合子结合。单克隆抗体2A 5和4 B6识别一个以上的蛋白质条带，通过免疫印迹检测到的鸡动合子上清。从受精后0 h开始，MAb 2A 5识别多种抗原;受精后10 h，MAb 4 B6也识别多种抗原。单克隆抗体1A 6识别一个单一的类似于17 kDa的蛋白，和2B 5识别一个单一的类似于32 kDa的蛋白在受精后15小时。在评估这些单克隆抗体对埃及伊蚊的鸡蛔虫感染性的影响的膜喂养试验中，将单克隆抗体1A 6和2B 5添加到感染性血粉中显著抑制蚊子中肠中的卵囊发育，相反，单克隆抗体2A 5似乎增强感染性。这些结果表明，疟原虫动卵细胞分泌的蛋白质（除了以前的特征几丁质酶），可能是阻断疟疾传播的目标。动合子分泌的中和敏感分子的未来调查应提供有价值的深入了解的机制，其中动合子退出血餐，渗透和横向围食基质，并侵入蚊子中肠上皮。
The development of transmission-blocking vaccines is one approach to malaria control. To identify novel Plasmodium zygote- and ookinete-secreted proteins as targets of blocking malaria transmission, monoclonal antibodies (MAbs) were produced against parasite-secreted proteins found in Plasmodium gallinaceum ookinete culture supernatants. Four MAbs-1A6, 2A5, 2B5, and 4B6-were identified that bound to P. gallinaceum zygotes and ookinetes in diverse patterns in terms of spatial localization on parasites, time course of antigen expression, and Western immunoblot patterns. MAbs 2A5 and 4B6 recognized more than one protein band as detected by Western immunoblot of A gallinaceum ookinete supernatants. Beginning at 0 h postfertilization, MAb 2A5 recognized a diverse set of antigens; at 10 h postfertilization, MAb 4B6 recognized several antigens as well. MAb 1A6 recognized a single similar to 17-kDa protein, and 2B5 recognized a single similar to 32-kDa protein at 15 h postfertilization. In membrane feeding assays to assess the effect of these MAbs on A gallinaceum infectivity for Aedes aegypti mosquitoes, the addition of MAbs 1A6 and 2B5 to infectious blood meals significantly inhibited oocyst development in the mosquito midgut, In contrast, MAb 2A5 seemed to enhance infectivity. These results demonstrate that Plasmodium ookinetes secrete proteins (in addition to previously characterized chitinases) that may be targets for blocking malaria transmission. Future investigation of ookinete-secreted neutralization-sensitive molecules should provide valuable insight into mechanisms by which ookinetes exit the blood meal, penetrate and transverse the peritrophic matrix, and invade the mosquito midgut epithelium.